Differential scanning calorimetry study of the interaction of antidepressant drugs, noradrenaline, and 5-hydroxytryptamine with a membrane model.
Differential scanning calorimetry was used to study the interaction of a membrane model with two neuromediators [noradrenaline and 5-hydroxytryptamine (Serotonin)] and four antidepressant drugs (imipramine, indalpine, citalopram, and milnacipran), known to be uptake inhibitors of these neuromediators. The study was carried out on dipalmitoyl phosphatidylcholine liposomes, a bilayer phospholipid system taken as a simplified model of biological membranes. Analysis of the thermograms led us to classify the molecules according to their lipophilic action, as in the conventional measurement of the water-octanol partition coefficient, and also enabled us to precisely determine their location along the phospholipid bilayer. A hypothesis based on this localization is put forward concerning the competitive, or otherwise, character of the blocking of uptake of the neuromediators. The extreme cases of interaction and localization of imipramine and milnacipran, a new antidepressant, relative to the bilayer are also analyzed in terms of side effects.
Bauer
M
M
Pierre Fabre Medicament, Pharmaceutical Research and Development, Castres, France.
Megret
C
C
Lamure
A
A
LaCabanne
C
C
Fauran-Clavel
M J
MJ
D015060:1,2-Dipalmitoylphosphatidylcholine; D000928:Antidepressive Agents / Q000737:chemistry*; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003521:Cyclopropanes / Q000737:chemistry; D007099:Imipramine / Q000737:chemistry; D008567:Membranes, Artificial; D000078764:Milnacipran; D008962:Models, Theoretical; D009638:Norepinephrine / Q000737:chemistry*; D000442:Octanols; D010880:Piperidines / Q000737:chemistry; D012701:Serotonin / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
D000928:Antidepressive Agents; D002021:Buffers; D003521:Cyclopropanes; D008567:Membranes, Artificial; D000442:Octanols; D010880:Piperidines; D015060:1,2-Dipalmitoylphosphatidylcholine; D012701:Serotonin; D000078764:Milnacipran; D007099:Imipramine; C018181:indalpine; D009638:Norepinephrine